The present invention relates generally to prevention of dental caries and more specifically provides: methods for lessening the cariogenicity of materials to be placed in the oral cavity; products, especially foodstuffs, treated according to such methods to have substantially diminished cariogenic effects when taken into the mouth; and methods and materials for treating the oral cavity to counteract or neutralize the effects of cariogenic materials present in salivary retention areas.
The incidence of dental caries is pandemic, resulting in enormous discomfort to dental patients and huge expenditures of monetary resources. The prior art is rich in proposals for prophylactic and restorative treatments respecting carious degradation of teeth. Such treatments may be grossly classified into two groups, (1) "localized" applications of materials directly to the mouth, and (2) "systemic" (generally dietary) treatments. Both groups of treatments focus on preserving the integrity of crystalline minerals from which the teeth are formed and consequently there often exists a degree of similarity in treating agents employed.
"Localized" treatments generally consist either of routine application of dental preparations (toothpastes, mouthwashes, and the like) which contain relatively dilute concentrations of various soluble and insoluble agents, or periodic administration of similar substances in more concentrated form. A first type of routine treatment has as its goal the reduction of population of flora and consists of application of bactericidal or bacteriostatic agents. Such treatments are not pertinent to the present invention.
Toothpastes routinely employed in the art may consist simply of abrasive materials whose function is to wear away dental plaque (see, e.g., U.S. Pat. No. 3,629,398), but more often toothpastes contain a wide variety of elements in combinations substantially duplicating the mineral content of the teeth. U.S. Pat. No. 4,048,300, for example, discloses dental creams containing, inter alia, abrasive minerals. The asserted function of such dental creams is to provide not only a source of plaque-removing abrasives, but also to topically "remineralize" exposed tooth surfaces which may have been selectively demineralized in early stages of caries formation. Many toothpastes include fluoride ion sources in low concentrations (see, e.g., U.S. Pat. No. 3,885,028) and recent reports have indicated that use of mouthwashes comprising a 0.2 percent solution of sodium fluoride is effective in reducing the incidence of dental caries in children.
The most common long-term periodic treatments are also aimed at "remineralization" and involve applying concentrated solutions and suspensions of one or more of the twenty-one elements ordinarily present in the tooth itself. Especially preferred treatments include fluorine salts or calcium and phosphate ion sources. U.S. Pat. No. 4,083,955, for example, discloses allegedly beneficial remineralization processes involving sequential application of separate compositions providing calcium ions or phosphate ions. U.S. Pat. No. 4,080,440 discloses application of a metastable, low pH, mixture of soluble sources of calcium and phosphate ions which preferably contains a source of fluorine ions. Both these types of applications specifically acknowledge a basic problem inherent in locally supplying calcium and phosphate ions to the tooth surface, i.e., the rapid formation of relatively insoluble (and ineffective) calcium phosphate or calcium fluoride salts upon admixing ion sources in solution. As another example, U.S. Pat. No. 3,978,206 discloses dental products and appliances made with ion exchange resins containing calcium, phosphate and fluorine ions, which resins are said to bypass the calcium phosphate and/or calcium fluoride precipitation problem.
"Systemic" treatments of the prior art are frequently aimed at maintaining and/or elevating "whole body" levels of calcium, phosphorous, fluorine and other elements in order to directly or indirectly provide an enhanced storehouse of materials for natural mineralization and, assertedly, remineralization of teeth. Treatment of water supplies to provide a dietary intake of fluorine on the order of one-half to one part per million is generally acknowledged as producing salutory cariostatic effects on children during the years of permanent tooth formation. Once teeth have been fully formed, however, such systemic fluoride treatments are generally held to be ineffective in preventing caries and, despite immense research efforts, the mechanism of action of fluorine in retarding tooth decay remains unclear.
Substantial efforts in the prior art have also been directed toward supplementing dietary intake of calcium, phosphorous and other elements, for the purpose of providing long term cariostatic effects. See, e.g., Limbustu, et al., J.D. Res., 39, No. 4, p.722 (1960); Dalderup, J.D. Res., 38, No. 6, pp. 1173-7 (1959); McClure, et al., J.D. Res., 38, No. 4, pp. 776-781 (1959); and McClure, et al., J.A.D.A., 58, pp. 36-41 (1959). Wynn, et al., J.D. Res., 39, No. 6, pp. 1148-1151 (1960) provides an excellent analysis of prior experimental studies on the cariostatic effects of various calcium and phosphorous supplemented diets, concluding the results are frequently contradictory for wholly unexplainable reasons. See also, Limbasuta, "Studies on the Prevention of Experimental Dental Caries in Rats with Calcium, Phosphate and Fluoride Compounds", M.S. Thesis, The University of Rochester, Rochester, N.Y., 1961.
The published literature in this area is currently said to contain over 100 reports of caries preventative action resulting from increased intake by experimental animals of phosphates, alone and in combination with other metal ions (including calcium) as well as in combination with a source of fluorine. Systemically administered phosphates are said to differ in cariostatic activity depending on the type of anion (cyclictrimeta-, hexameta-, ortho-, and pyrophosphate, increasing in effectiveness in that order). Compounds of the same phosphate series are also said to vary in activity depending on the cation (hydrogen, sodium, potassium, ammonium, calcium and magnesium, decreasing in that order. The more pertinent studies of this type have indicated that cariostatic effects of phosphates appeared to be due in part to direct action of phosphate on the teeth as food passes through the mouth, as well as to the return of phosphate to the mouth as a salivary constituent. See, "Minerals: Calcium and Phosphorus" by R. S. Harris, appearing in "Dietary Chemicals vs. Dental Caries" Advances in Chemistry Series, 94, at pp. 116-122 (American Chemical Society, Washington, D.C. 1970).
Also pertinent to the background of the invention are prior art proposals for solubilization of normally insoluble phosphates to facilitate their transport and utilization in biological systems. U.S. Pat. Nos. 3,375,168 and 3,494,916, for example, are directed to methods for forming solubilized complexes of sugars and inorganic phosphates. Such complexes are said to be useful both in remineralization of teeth (when incorporated in toothpastes) and as components as cariostatic diets. As another example, U.S. Pat. No. 4,022,887 treats the preparation of edible cyclotriphosphates and cyclotetraphosphates and their asserted use as phosphorous supplements in caries-inhibiting diets.
The above-noted prior art developments have unfortunately resulted in only minor advances in prevention of carious degradation of teeth. To date, none of the alleged short term or long term "remineralization" processes has been shown to be consistently effective and, with the possible exception of water fluoridation, none of the proposed dietary supplementation schemes has uniformly resulted in significant reduction in the incidence of dental caries. Indeed, in many instances the proposed methods and materials have proven to have deleterious side effects. Long term exposure to water having fluorine levels of ten parts per million or more results in mottling of teeth. Indeed, great care must be taken in administering concentrated sodium and stannous fluoride to teeth in order to avoid poisoning of the patient.
As further background to the present invention it is to be noted that dental enamel (the hard, glistening substance covering the exposed portions of the teeth) is composed chiefly of hydroxypatite with small amounts of carbonate, magnesium, fluoride and an organic matrix (about 0.5 percent) of glycoprotein and a keratin-like protein. Structurally, enamel is made up of oriented rods, each of which consists of a stack of rodlets encased in an organic prism sheath. Carious dental enamel is generally recognized to result from the selective dissolution of apatite crystallites of varying size and shape.
In vitro model studies by the inventor and his co-workers have established that the selective demineralization of intact enamel resembling in vivo dental caries is accomplished not simply by acid treatment but by, e.g., exposure to aqueous inorganic and organic acid solutions which are less than fully saturated with calcium and phosphate ions.
The dissolution/demineralization process in such systems is generally seen to continue until the acid medium in contact with the tooth surface becomes essentially saturated with dissolved calcium and phosphate ions, whereupon dissolution ceases unless events occur which again bring about a relative unsaturation of the aqueous medium. If, for example, it occurs that the acidity of the medium is increased (either by addition of hydrogen ions directly or by formation of hydrogen ions by salivary flora) the demineralization process will again be initiated. Within this context one can envision the following model of the events leading up to carious degradation of enamel surfaces.
In the oral cavity, enamel surfaces are continuously bathed with salivary fluid which normally has a pH within the range of 6.5 to 7.5 and is essentially saturated with calcium ions (about 0.058 mg/ml) and phosphate ions (about 0.168 mg/ml). No dissolution of enamel will ordinarily occur unless the pH of the saliva in direct contact with the tooth surface is reduced, resulting in relative unsaturation with calcium and phosphate ions. Decreases in salivary pH may occur rapidly, as when highly acidic material is taken into the mouth, or relatively gradually, as when salivary flora metabolize refined sugar and other carbohydrates. Owing to the constant flow of salivary fluid into the mouth, the aforementioned gradual pH changes seldom occur in saliva contacting fully exposed enamel surfaces. Gradual changes frequently occur, however, in so-called "small spaces" or "salivary retention areas", i.e., areas of contact between adjacent teeth or between dental or orthodontic appliances and teeth, small pits or grooves in enamel surfaces, and at the site of adherence of dental plaque.
As a result of experimental work by the inventor and his co-workers, it has long been accepted that hydrostatic forces affecting fluids in these confined spaces substantially preclude the physical displacement of retained saliva by ordinary parotid fluid flow. Bacterial fermentation of sugars and the like is thus permitted to proceed in these spaces essentially undisturbed and can result in dramatic pH drops in retained saliva within a matter of minutes or hours depending upon the bacterial count within the narrow space, even though salivary flow in the mouth is altogether normal. Such drops in pH, as noted above, provide an environment conducive to selective dissolution of enamel.
The cariogenicity of fluids retained in salivary retention areas is further enhanced by osmotic forces extant in the oral cavity. Oral intake of foods having soluble refined sugars and other cariogenic substances will, of course, result in enhancement of food supplies for bacteria in salivary retention areas. Despite the general inability of flowing saliva to displace retained saliva, osmotic differentials between "trapped" saliva and saliva containing dissolved sugars will result in migration of these bacterial nutrients into salivary retention areas. To the extent that there is a tendency for dissolved sugars and the like to migrate from salivary retention areas across hydrostatic force barriers and into fresh flowing saliva (thereby effecting a depletion of bacterial food supplies) so also is there a tendency for retained fluids to be similarly depleted of their "normal" complement calcium and phosphate ions because the ions migrate along with the osmotically active substances. This results in an amplification of unsaturation of retained saliva with respect to these ions, so that fluids of even moderately low pH will have more extensive cariogenic effect. In sum, both hydrostatic and osmotic force effects in the mouth tend to create a medium in the salivary retention areas which is particularly conducive to carious degradation of enamel. Indeed, it is precisely in these areas that the highest incidence of dental caries is encountered. Similarly, the most highly cariogenic foodstuffs have been found to be acidic fluids having high concentrations of refined sugars in a dissolved state.
Review of prior art developments within the context of the above analysis of events taking place in the oral cavity provides an explanation for the very limited successes that have been achieved in the art. Simply put, none of the prior proposals have adequately taken into consideration and accommodated for the dynamic hydrostatic and osmotic forces at the localized level of salivary retention areas within the mouth. Apart from bactericidal compositions which inhibit bacterial propagation upon transport of active agents into these areas, none of the prior art localized treatments have been designed to mitigate the adverse effects of bacterial proliferation in terms of decreased pH and consequent calcium and phosphate ion "imbalances". Further, no prior art methods and materials have had as their focus the "neutralization", prior to oral intake, of the ion-imbalancing, cariogenic effects of foodstuffs containing refined sugars and other soluble carbohydrates.